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Special Article - Trauma Early Versus Late Post-Traumatic Venous Thromboembolism; An Elapsed Time Controversy and Risk Factors Elsayed YMH1* DVT event [2]. Knudson et al. [2] agree with this interpretation and Critical Care Unit, Fraskour Central Hospital, Egypt their hypothesis [7]. *Corresponding author: Yasser Mohammed Hassanain Elsayed, Critical Care Unit, Fraskour Central PE is generally thought to occur days after the acute [1]. Hospital, Damietta Health Affairs, Egyptian Ministry of In 2007, Menaker et al. [1] hypothesized that PE often occurs early Health (MOH), Damietta, Egypt after injury. They sought to elucidate the timing of PE after trauma. From 2007 to 2018 literature publications, there were five large post- Received: October 11, 2019; Accepted: October 14, 2019; Published: October 21, 2019 traumatic venous thromboembolism studies [3,4,6,9,10]. (Table 1). All the five studies signify the difference between early and late Editorial pulmonary [3,4,6,9,10]. Otherwise, Kazemi et al. [9] study that conducted in the Intensive Care Unit (ICU), all studies were Unfortunately, after reviewing literatures over the past twelve done in Level I [3,4,6,10]. years, the author found that there was no fixed definition for either “early” or “late” post-traumatic Pulmonary Embolism (PE). Indeed, Bahloul et al. [7]. So, according to the above studies, the definition post-traumatic Venous Thromboembolism (VTE) that includes both for an early PE was varies from less than two days (Gelbard et al. [3]), PE and Deep Venous Thrombosis (DVT) remains a major problem and to less than three days (Benns et al. [6], Coleman et al. [4], and Kazemi a large challenge in cardio-pulmonary diseases. PE remains relatively et al. [9]), to less than four days (Brakenridge et al. [10]) for occurrence common after trauma [1]. PE is a well-recognized potentially fatal of pulmonary embolism after trauma (Table 2). And, the definition complication after trauma [1]. Despite compliance with prophylactic for the late PE actually will be the larger values than the previous for measures, PE remains a threat to post-injury recovery [2]. Post- early PE [3,4,6,9,10]. Thus, the range of elapsed time for occurrence of traumatic pulmonary embolic events are associated with significant pulmonary embolism after injury is 2-4 days [3,4,6,9,10]. morbidity [3]. The reported incidence of PE after trauma has more However, these studies considered multiple risk factors for than doubled in recent years. But, the PE-accompanied mortality evaluation and assessment the cases of post-traumatic venous has remarkably decreased, suggesting that we are identifying a thromboembolism. Indeed, the risk factors for posttraumatic PE different disease entity or stage [2]. PE is also well-known to cause might be different from those for Deep Venous Thrombosis (DVT) significant morbidity and mortality after injury [4]. There are higher [2]. Trauma produces from time-dependent responses from the frequency of DVT in post-traumatic critically ill patients [5]. Despite haemostatic system can increase the risk of bleeding of an injury the high frequency of DVT in post-traumatic critically ill patients, which needs blood transfusion7. However, it has been well-established symptomatic PE remains, although not frequently observed, because that the cases with hemorrhagic shock and/or those which required systematic screening is not performed [5]. blood transfusion are highly associated with the development of an Currently, an early PE after trauma may occur with variant early PE [8]. Worthily, there are numerous risk factors implicated underlying pathophysiology than previously thought [6]. In fact, the in these studies. The following risk factors linked to timing of early inflammatory process that is initiated by a chest trauma may be forced versus late post-traumatic PE [3,4,6,9,10]: by a coexisting tissue hypoxia and systemic inflammation (usually • Age associated with severe injury) leading to pulmonary endothelial damages and in situ thrombosis of pulmonary arteries [7]. In addition, • Long severe trauma increases the levels of pro-inflammatory pro-coagulant • Brain injury cytokines, leading to an inflammatory reaction [7]. Although early acute traumatic coagulopathy has received much recent attention, the • procoagulopathy that often follows appears less appreciated [8]. In • Severe (ISS) the more advanced studies using thromboelastography indicate that patients are at risk for hypercoagulability early after injury4. Hypoxia • Chest AIS more than 3 early after injury is often ascribed to other causes [1]. Indeed, • RV dysfunction Knudson et al. [2], had postulated the ability of a major chest trauma in stimulating inflammation which lead to the direct formation of • Hospital length of stay (LOS) PE by direct inflammation of pulmonary vessels. This theory may • Transfusions explain why is associated with PE, but not significantly with DVT. In fact, only 20% of the patients with PE had an associated • DVT Prophylaxis.

Thromb Haemost Res - Volume 3 Issue 3 - 2019 Citation: Elsayed YMH. Early Versus Late Post-Traumatic Venous Thromboembolism; An Elapsed Time Submit your Manuscript | www.austinpublishinggroup.com Controversy and Risk Factors. Thromb Haemost Res. 2019; 3(3): 1031. Elsayed. © All rights are reserved Elsayed YMH Austin Publishing Group

Table 1: Showing the major post-traumatic venous thromboembolism studies. Issue Brakenridge et al. [10] Benns et al. [6] Coleman et al. [4] Gelbard et al. [3] Kazemi et al. [9] • Informative data • Year of study 2011 2014 (2005-2010) 2015 (2007-2013) 2016 (2008-2013) 2018 • Site of study Level I trauma center Level I trauma center Level I trauma center Level I trauma center ICU • No. of total patients 17,736 (108 PE) 6,483 (54 PE) 54,964 (144 PE) NA (50 PE) 240

• Risk factors: • Age - - - - More early PE • Long bone fracture More early PE More early PE More early PE - More early PE • Brain injury More late PE More late PE More late PE - - • Spinal cord injury - - More late PE - - • Severe ISS More late PE More late PE More late PE - More early PE • Chest AIS >3 More late PE - - - - • RV dysfunction - - - More early PE - • Hospital LOS - More early PE - - - • Transfusions - - More late PE - - • DVT Prophylaxis More late PE More late PE - - - • Results • % of early PE 50% 35% 42.9% 28% 40.4% • % of Late PE 50% 65% 57.1% 72% 59.6% AIS: Abbreviated Injury Score; DVT: Deep Venous Thrombosis; ISS: Injury Severity Score; LOS: Length Of Stay; PE: Pulmonary Embolism; RV: Right Ventricle

Table 2: Showing the timing for major post-traumatic PE studies. Study Year of study Timing for early PE Timing for late PE 1. Brakenridge et al. [10] 2011 within four days More than four days 2. Benns et al. [6] 2005-2010 within three days More than three days 3. Coleman et al. [4] 2007-2013 within three days More than three days 4. Gelbard et al. [3] 2008-2013 within two days More than two days 4. Kazemi et al. [9] 2018 within three days More than three days PE: Pulmonary Embolism In 2011 impact on early PE [4]. Brakenridge et al. [10] study was the first to clears risk factors In 2016 which were accompanied to the timing of a post-traumatic PE. The Gelbard et al. [3] retrospective study, reported that the Computed only independent and highest risk factor for early PE was the long Tomographic (CT) effects for all patient of traumatic injury with bone extremity fractures. But, the late PE groups had a higher ISS, possible PE. CT measurement can be predictive for Right Ventricular severe , severe chest injury, and a delay in the chemical (RV) dysfunction. The primary targets for the study were PE-related prophylaxis initiation around 24 hours. The benefits of immediate mortality and its relation with RV dysfunction. They found RV prophylaxis may outweigh risks. Patients with severe head pathophysiological changes with post-traumatic PE. But the early appear to have later PE events10. post-traumatic PE appears to be associated with fewer RV changes In 2014 than the late post-traumatic PE and may be representative of primary Benns et al. [6] reported that the occurrence of early PE more pulmonary thrombosis. Whatever, patient sustaining a late PE had a suggested than late PE. This despite larger difference of clinical entity higher PE-related mortality rate (16.7% vs. 0%), larger RV diameters, in the early PE than the late PE. They found that the early PE patients RV/LV volume ratio, RV volumes, and RV/LV diameters ratio [3]. were more likely to have; lower extremity injuries, ISS, less likely Yet, they set out to demonstrate that early PE is not accompanied to undergo the operative interventions, less likely for femoral vein to a RV dysfunction when using a CT measurement, and suggested cannulation, and shorter average LOS. In contrast, late PE patients that early PE may have a different underlying pathophysiology. who had suffered from a had more delay in Indeed, there was controversy in the outcome for both early and initiating chemical prophylaxis [6]. late PE and in embolic management of CT findings for early PE. However, it remains unclear whether these physiologic effects or In 2015 clinical outcomes differ between early (<48 hours) vs late (≥48 hours) Coleman et al. [4] showed that there were specific injury patterns, post-traumatic PE. Thus, there were no significant differences in the such as an extremity abbreviated injury score (AIS) >3, were predictive baseline characteristics nor in injury patterns between the early and of early PE. Whereas, a severe head injury and spinal cord injury were late PE groups [3]. linked to a higher risk of late PE, as well as, blood transfusions and In 2018 high ISS. Kazemi et al. [9] study identified the factors linked to traumatic PE The study used thromboelastography as an indicator for the in the Emergency Ward. They concluded that the occurrence of early 4 patients that are at risk for hypercoagulability early after injury . PE can be predicted in a majority of the trauma-patients who were Despite this risk, prophylactic anticoagulation is often delayed requiring ICU admission especially older patients, patients with long in patients with certain injuries due to concerns about bleeding. bone fractures and those with severe injury. This study has confirmed Unfortunately, the timing of prophylactic anticoagulation had no that the patients in early PE group were older than those who suffered

Submit your Manuscript | www.austinpublishinggroup.com Thromb Haemost Res 3(3): id1031 (2019) - Page - 02 Elsayed YMH Austin Publishing Group late PE (45.9±7.49 vs. 42.6±8.81 years; P=0.002). In addition, the 3. Gelbard RB, Karamanos E, Farhoomand A, Keeling WB, McDaniel MC, prevalence rate of long bone fractures in lower extremities was Wyrzykowski AD, et al. Immediate post-traumatic pulmonary embolism is not associated with right ventricular dysfunction. Am J Surg. 2016; 212: 769-774. significantly higher in those with early PE when compared with the other patients (26.8% vs. 7.0%, P<0.001). Finally, they found that the 4. Coleman JJ, Zarzaur BL, Katona CW, Plummer ZJ, Johnson LS, Fecher A, et al. Factors Associated with Pulmonary Embolism Within 72 Hours of group with early stage PE had more severe injuries when compared to Admission after Trauma: A Multicenter Study. J Am Coll Surg. 2015; 220: those with late PE (P=0.007) [9]. 731-736. Conclusion and Recommendations 5. Bahloul M, Chaari A, Dammak H, Medhioub F, Abid L, Ksibi H, et al. Post- traumatic pulmonary embolism in the intensive care unit. Ann Thorac Med. The author think that if the further studies confirm the presence 2011; 6: 199-206. of unsuspected early PE, all admitted trauma patients should be re- 6. Benns M, Reilly P, Kim P. Early pulmonary embolism after injury: A different evaluated for a hypercoagulability after trauma. Further studies are clinical entity? Injury. 2014; 45: 241-244. indicated as this has implications concerning the prevention of PE in 7. Bahloul M, Dlela M, Bouaziz NK, Turki O, Chelly H, Bouaziz M. Early post- trauma patients. Unfortunately, the timing of early VTE versus late traumatic pulmonary-embolism in patients requiring ICU admission: more VTE is still controversial issue for further decisive study. complicated than we think!. Editorial. J Thorac Dis. 2018; 10: S3850-3858. 8. Holley AD, Reade MC. The ‘procoagulopathy’ of trauma: too much, too late? Acknowledgement Curr Opin Crit Care. 2013; 19: 578-586.

The author wishes to thank Editor-in-chief and editorial board to 9. Kazemi DF, Jafari ZMA, Torabi GZ, Namdar P. Prevalence and main give me the chance for submission of an editorial article. determinants of early post-traumatic thromboembolism in patients requiring ICU admission. Eur J Trauma Emerg Surg. 2018; 44: 133-136. References 10. Brakenridge SC, Toomay SM, Sheng JL, Gentilello LM, Shafi S. Predictors 1. Menaker J, Stein DM, Scalea TM. Incidence of early pulmonary embolism of early versus late timing of pulmonary embolus after traumatic injury. Am J after injury. J Trauma. 2007; 63: 620-624. Surg. 2011; 201: 209-215. 2. Knudson MM, Gomez D, Haas B, Cohen MJ, Nathens AB. Three thousand seven hundred thirty-eight posttraumatic pulmonary emboli: a new look at an old disease. Ann Surg. 2011; 254: 625-632.

Thromb Haemost Res - Volume 3 Issue 3 - 2019 Citation: Elsayed YMH. Early Versus Late Post-Traumatic Venous Thromboembolism; An Elapsed Time Submit your Manuscript | www.austinpublishinggroup.com Controversy and Risk Factors. Thromb Haemost Res. 2019; 3(3): 1031. Elsayed. © All rights are reserved

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